COVID-19 - Facts and Information Only Topic

[BillsFan4]

 

 

[Hapless Bills Fan]

Cloth Masks are 1918 Technology.

Health Care Workers in 2020 should not be expected to treat infectious patients whilst wearing them.

https://bmjopen.bmj.com/content/5/4/e006577?fbclid=IwAR2AOLJ89NahTECuIMPmXXfzSRgGIijFgy_3JFcoPpeTotMDE57zKX1jVbM

"Penetration of cloth masks by particles was almost 97% and medical masks 44%." (note "medical masks" are the ordinary pleated paper kind)

 

20 hours ago, OldTimeAFLGuy said:

...so why is this being largely ignored?....out for groceries today and multiple folks wearing masks or facial scarf?....why so Hap?...

 

OK this is gonna squirm a bit beyond "just the facts" but I'll try.  Probably too verbose.

1) There's wearing and wearing, right?

If you want a barrier to remind you to not touch your face, or to help protect you from the random loogie someone hocks as they walk past and the wind carries it into your face (hate when that happens), Anything Goes.  Paper medical mask, dust mask, fabric mask, bandana.    People aren't always sensible about using masks - lift them to smoke, punch holes in them to drink through a straw, reach under them to scratch an itch or worse (as though the mask itself has magical protective properties).  Fabric masks will get wet faster and then may conduct virus and bacteria through the fabric towards your face, and they have just been found (in the link above) to simply not be very effective.  But the democracies that have done the best job containing covid-19 have a cultural tradition of public mask-wearing (Taiwan, Singapore, S. Korea, Japan) and today almost everyone on their streets is wearing a mask.  That may not be coincidence, although they are doing many other things (widespread testing, etc).  But overall, masks reduce the chance a sick person will transmit the disease. IMO it would be great if everyone wore one, just learn how to do it correctly - and fabric masks without a filter added are not effective.

On the other hand, if you are a health care worker in close contact with known infected people 24/7, you need more than a casual barrier.  You need a respirator grade mask (N95 or better) that is certified to remove 95% or more of the particulates.  Truthfully, for close contact and disease prevention, it's not enough protection! but it's the minimum acceptable standard.

 

2) We have a critical shortage of N95 respirator masks for health care workers, so standards have been "relaxed".  HCW are being told they can wear surgical masks, paper masks, or even make their own fabric filter-holders for inadequate paper filters.  This is SHAMEFUL, IMO.  It is asking brave men and women to who are risking their own health and lives to help people as HCW and first responders, to operate in 1918 conditions - but it's 2020. 

 

In part, it's because, just as we didn't push the "fast track" option on covid-19 test development as some other countries did, we also didn't push the "fast track" on mask supply and production.  Taiwan, Singapore etc just requisitioned all the N95 masks and surgical masks in the country and controlled their distribution to hospitals and HCW first.  They also immediately requested manufacturers to scale up production and even put their equivalent of "national guard" to work producing them asap as I understand it.

And then yes, too, people are buying up and hoarding N95 masks.  Probably so they can punch holes in them to smoke and drink through straws.

Sorry for the squirm past the facts.  I may regret this and move the posts to the other thread if too much discussion ensues, we'll see.

So in part, IMO, the CDC's advice to the public on mask-wearing (do not wear masks) is influenced by supply-chain necessity.  We are trying to preserve supplies for HCW by discouraging the general public from wearing at least the N95 respirator masks, the minimum realistic disease-precaution for HCW and first responders.  The medical advice of doctors and CDCs in other countries is actually to citizens to please wear a mask (but an inexpensive paper one that suffices against casual contact)

Edit: FWIW, here is a Guardian (UK) article about Coronavirus myths that addresses masks.  Note they are talking about masks that trap particles, which cloth masks do NOT (see link bmj link above)

Claim: ‘Face masks don’t work’

Wearing a face mask is certainly not an iron-clad guarantee that you won’t get sick – viruses can also transmit through the eyes and tiny viral particles, known as aerosols, can penetrate masks. However, masks are effective at capturing droplets, which is a main transmission route of coronavirus, and some studies have estimated a roughly fivefold protection versus no barrier alone (although others have found lower levels of effectiveness).

If you are likely to be in close contact with someone infected, a mask cuts the chance of the disease being passed on. If you’re showing symptoms of coronavirus, or have been diagnosed, wearing a mask can also protect others. So masks are crucial for health and social care workers looking after patients and are also recommended for family members who need to care for someone who is ill – ideally both the patient and carer should have a mask.

However, masks will probably make little difference if you’re just walking around town or taking a bus so there is no need to bulk-buy a huge supply.

That nicely captures the paradox of the mask advice in US/UK: they are acknowledged to be effective at preventing both transmission (if you are the one who is asymptomatically or presymptomatically ill) and infection (if you are on the bus or in a checkout-line with someone who is ill).  But then they say it will make little difference in those circs so don't buy a bunch and wear 'em. 

 

 

[Saxum]

Commerce Department issued official mandatory telework policy.

 

Mandatory Telework

Effective Monday, March 23 at 12:01 AM EST, all telework-eligible Department employees are required to telework until further notice. Only mission critical employees may enter their normal worksite and only if necessary. Employee-specific questions should be directed to supervisors.

 

They also created a website for commerce just on virus:

https://www.commerce.gov/covid19employeeupdates

 

[Edit: per perusing their website, the driver for this is they had several covid-19 positive tested employees]

 

----------------------

 

They also have been warning about spoofs:

 

Attached is an example of one phishing campaign that has been reported in the media. It should be noted that organizations such as the WHO will never ask users to log in to verify safety information, send unsolicited emails, email attachments, request that you visit a website, or solicit donations.

 

Actual Phishing Scam Sample

 

[Edit: if you guys have clicked any of the links here, a key feature is that they do NOT require downloading anything.  They take you right to the info.

Being asked to download anything to get info on the pandemic is a HUGE RED ALERT, DON'T]

[Sundancer]

https://covidtracking.com/data/

 

US data compiled by state. Better versions to come for sure. 

 

Just now, Hapless Bills Fan said:

This is a good site, Thanks.  But oh, HAHAHAHAHA my first thought was "What, another arbitrary and unexplained grading system?  To The Dean, no I didn't

 

54 minutes ago, The Dean said:

Did you notice anything that explains their grading (A, A-, B, etc) of the states?

[BillsFan4]

6 hours ago, OldTimeAFLGuy said:

...so why is this being largely ignored?....out for groceries today and multiple folks wearing masks or facial scarf?....why so Hap?...

Hapless is definitely the one to ask but I’ll try to help.

 

https://www.health.com/condition/infectious-diseases/n95-respirator-mask-coronavirus

 

Quote

Infectious disease expert Amesh A. Adalja, MD, senior scholar at the Johns Hopkins Center for Health Security, tells Health that the N95 is still the recommended face mask for health professionals, because it has the capacity to filter out very small particles that could possibly contain the virus. “This is different than a surgical mask, which can only stop larger droplets,” says Dr. Adalja.

 

The N95 is designed to achieve "a very close facial fit," according to the Food and Drug Administration, and if properly fitted blocks "at least 95%" of very small test particles, though it doesn't completely eliminate the risk of illness, per the FDA.

 

They are actually trained how to wear+breath in these masks and how to properly remove+dispose them, etc. It can be difficult to breath for much more than 30 mins at a time (making them less practical for public use).

 

Quote

Right now, the advice from the CDC is that health care workers use “respiratory protection (i.e., a respirator) that is at least as protective as a fit-tested NIOSH-certified disposable N95 filtering facepiece respirator before entry into the patient room or care area.” Additionally, all staff should be medically cleared and fit-tested if using a disposable N95 mask and trained in the proper use, safe removal, and disposal of the mask.

 

 

It has to be a specific type of mask to be able to filter very small particles and must be worn properly at all times to offer protection.

 

But, in my opinion it’s still not the worst idea to wear a cloth mask in public, just for the simple reason that it will keep you from accidentally touching your nose/mouth (most common way to get sick). And it may help slightly contain your cough/sneeze droplets but I’m not really sure on that (that may not be true, I don’t know and I don’t want to offer any incorrect info).

 

Here’s the CDC FAQ on masks:

https://www.cdc.gov/niosh/npptl/topics/respirators/disp_part/respsource3healthcare.html

Edited March 22, 2020 by BillsFan4
Spelling error

[Cripple Creek]

(feel free to move if inappropriate here)

 

Are we listening?  Gallup Poll:

 

https://news.gallup.com/poll/297035/americans-rapidly-answering-call-isolate-prepare.aspx

[Edit: interesting, but this is a situation where a "majority" will not suffice.  But it helps us figure out where we are in the "reduction of social interactions" epidemic impact curves]

[Cripple Creek]

 

[Hap sez: I knew her in grad school.  Very ambitious person but knows her *****.  Her information is good, and so is her presentation]

Edit: OK, I have a bit of a quibble with her enthusiasm over approval of the FDA approval of the Cepheid covid-19 test today, calling it a "point of care" test.  It requires Cepheid's specialized machine of which there are 5,000 in the US at present, per Cepheid's website.

 

 

[Deranged Rhino]

In our age of disinformation, an important thread to keep in mind. 

 

[Edit: Thank you for the reminder.  One motivation for starting/maintaining this thread is as a source of vetted information.   I would be happy to hear of any inaccuracies [PM please], but so far all the PM's I get say something like "I have a friend who's a doctor/scientist/epidemiologist and I haven't found anything that disagrees"]

[Hapless Bills Fan]

Memo to Young People:  The Machine Gun Kelly "Voices in the Air" you hear Calling you to Mix and Mingle might be covid-19 virus particles.

 

https://www.statnews.com/2020/03/18/coronavirus-new-age-analysis-of-risk-confirms-young-adults-not-invincible/
"The new data show that up to one-fifth of infected people ages 20-44 have been hospitalized, including 2%-4% who required treatment in an intensive care unit."

(note that by "one-fifth of infected people" they mean "one-fifth of positive covid-19 tests" as the actual number of infected people is currently unknown)

Translation: Look at contracting covid-19 as a 1 in 5 chance that you wind up in hospital for weeks and will take more weeks or months to recover.

 

Article referenced:

https://www.medrxiv.org/content/10.1101/2020.03.15.20036293v1.full.pdf

Take home: Italy has more old people than Korea and also a social tradition of regular, close contact between generations which may be a factor in Italy's higher death rate. (overloaded hospitals and having to choose who gets the ventilator is also a factor)

[T&C]

This is actually a very good idea... give everyone in your neighborhood two pieces of construction paper or whatever, one red.. one green.

Especially helpful for the elderly. Green in the window is all is good... Red signals some sort of help needed.

14 hours ago, Foxx said:

O - for good. X - for not good. [because many are red/green colorblind]

13 hours ago, SDS said:

are cell phones out? ?

12 hours ago, Hapless Bills Fan said:

At least in these parts, many low-income elderly do not have cell phones.  Many no longer have landlines either.

If you're struggling to pay rent and utilities and getting food from food pantries, every extra goes.

If they do have an inexpensive cell phone, they may or may not be able to hear it (my mother is hard of hearing and could not hear hers)

 

They depend on relatives, church families, and social agencies checking on them in person. Now that's unsafe.
I'm actually going to suggest this to my neighbor who works with United Way/St. Vincent de Paul (and tells me these things 'cuz I wouldn't know otherwise)

Edited March 23, 2020 by Hapless Bills Fan
combine several posts and decrease photo size

[Hapless Bills Fan]

From @SDS:

 

https://www.epa.gov/coronavirus/coronavirus-and-drinking-water-and-wastewater

 

Key excerpt:

"The COVID-19 virus has not been detected in drinking-water supplies. Based on current evidence, the risk to water supplies is low. Americans can continue to use and drink water from their tap as usual.  EPA has established regulations with treatment requirements for public water systems that prevent waterborne pathogens such as viruses from contaminating drinking water and wastewater. Coronavirus, which causes COVID-19, is a type of virus that is particularly susceptible to disinfection and standard treatment and disinfectant processes are expected to be effective."

 

 

 

 

 

[Hapless Bills Fan]

On 3/23/2020 at 8:38 AM, BringBackFergy said:

https://techcrunch.com/2020/03/19/french-study-finds-anti-malarial-and-antibiotic-combo-could-reduce-covid-19-duration/

 

 

This is the same French physician study of 25 patients lauded by Dr Oz and touted in press conference by President Trump.  While we're at it let's bite the snake: https://video.foxnews.com/v/6144015101001#sp=show-clips

 

Pump the brakes.

[edit: a couple posts down from this, I found the preprint of the actual paper and discuss]

 

1) Clinical outcomes are not published yet.  That's really the bottom line of what's needed here - if the patients are severely ill, will it prevent them from becoming critically ill?  If they are critically ill, will it improve their outcome?  [China, which asserts similar studies, has also not made their study design or results available

2) If it's 25 patients, that's 8 patients per arm

3) the graph does not contain error bars - nor does it indicate how many patients were tested by PCR.  1 per line?  All 8?

4) Randomized, double blind controlled studies are important because time after time, it has been shown that open (the HCW know), non controlled studies on very small patient populations do not hold up in larger patient populations.  That's really a hard lesson learnt in false hope and sometimes blood, folks.

 

Z-pack is an important antibiotic - Drs try to restrict its use to save bacterial resistance from developing.  Hydroxyquinolone is used to treat lupus and other autoimmune diseases.  Now that Dr Oz and Trump have puffed up this study, Lupus and Rheumatoid Arthritis patients already can not obtain the hydroxyquinalone they depend on to keep their disease in check.

 

Hydroxyquinolone causes serious side effects including cardiac arrhythmias (you drop dead).  The therapeutic window is narrow. 

Azythromycin (Z-pack drug) also has cardiac side effects, which may be additive
 

Now fearful people who may not need medication at all for their covid-19 illness (or may not have covid-19, but flu or other virus) will be taking them, putting themselves at risk and depriving patients who need them

 

I do not have words for what I'd like to do here.  Well, actually I do, but I'm trying to do deep breathing exercises and channel calm.

I know no ill of the French physician and he is apparently on the front lines trying to cope with this crisis - note this is NOT coming from WHO or the French CDC as one would expect of a true miracle breakthrough.

Dr Oz has a long history of peddling false cures on scant evidence.

 

[BillsFan4]

 

 

[BringBackFergy]

2 hours ago, Hapless Bills Fan said:

 

This is the same French physician study of 25 patients lauded by Dr Oz and touted in press conference by President Trump.  While we're at it let's bite the snake: https://video.foxnews.com/v/6144015101001#sp=show-clips

 

Pump the brakes.

 

1) Clinical outcomes are not published yet.  That's really the bottom line of what's needed here - if the patients are severely ill, will it prevent them from becoming critically ill?  If they are critically ill, will it improve their outcome?  [China, which asserts similar studies, has also not made their study design or results available

2) If it's 25 patients, that's 8 patients per arm

3) the graph does not contain error bars - nor does it indicate how many patients were tested by PCR.  1 per line?  All 8?

4) Randomized, double blind controlled studies are important because time after time, it has been shown that open (the HCW know), non controlled studies on very small patient populations do not hold up in larger patient populations.  That's really a hard lesson learnt in false hope and sometimes blood, folks.

 

Z-pack is an important antibiotic - Drs try to restrict its use to save bacterial resistance from developing.  Hydroxyquinolone is used to treat lupus and other autoimuneNow that Dr Oz and Trump have puffed up this study, Lupus and Rheumatoid Arthritis patients already can not obtain the hydroxyquinalone they depend on to keep their disease in check.

 

Hydroxyquinolone causes serious side effects including cardiac arrhythmias (you drop dead).  The therapeutic window is narrow. 

Azythromycin (Z-pack drug) also has cardiac side effects, which may be additive
 

Now fearful people who may not need medication at all for their covid-19 illness (or may not have covid-19, but flu or other virus) will be taking them, putting themselves at risk and depriving patients who need them

 

I do not have words for what I'd like to do here.  Well, actually I do, but I'm trying to do deep breathing exercises and channel calm.

I know no ill of the French physician and he is apparently on the front lines trying to cope with this crisis - note this is NOT coming from WHO or the French CDC as one would expect of a true miracle breakthrough.

Dr Oz has a long history of peddling false cures on scant evidence.

 

It seems this drug is gaining traction (not as a "cure" but as a way to shorten the severity of the virus).  The article cites a Chinese study published so I guess we can either believe their data or call it hogwash. University of Minnesota doing their own study, as are South Korea and Spain. The WHO has gotten on board to at least investigate the usefulness of the drug so that's promising.

 

Sadly, some medical facilities have run out of the drug not based on demand, but some physicians and pharmacists "hoarding" the drugs for friends and family (at least that's the allegation).

 

 

https://www.statnews.com/pharmalot/2020/03/19/teva-mylan-coronavirus-covid19-malaria/

 

 As a result, Mylan plans to restart production of hydroxychloroquine tablets at a West Virginia facility to meet “potential” increased demand and is looking to begin manufacturing outside the U.S. in coming weeks, according to a statement. In explaining its decision, the company noted the World Health Organization listed the drug as being under investigation for combating the coronavirus.

 

He also pointed out that the University of Minnesota announced that it will start a multi-center study evaluating hydroxychloroquine in around 1,500 people who were exposed to Covid-19 within three days but are not symptomatic. And Amsellem also noted that studies are under way in South Korea and Spain.

 

And a search of PubMed, an online database of medical papers, turns up several abstracts, including “Discovering drugs to treat coronavirus disease 2019 (COVID-19),” published by three Chinese researchers in Drug Discoveries & Therapies. 

 

 

[Hapless Bills Fan]

1 hour ago, BringBackFergy said:

It seems this drug is gaining traction (not as a "cure" but as a way to shorten the severity of the virus).  The article cites a Chinese study published so I guess we can either believe their data or call it hogwash. University of Minnesota doing their own study, as are South Korea and Spain. The WHO has gotten on board to at least investigate the usefulness of the drug so that's promising.

 

Sadly, some medical facilities have run out of the drug not based on demand, but some physicians and pharmacists "hoarding" the drugs for friends and family (at least that's the allegation).

 

https://www.statnews.com/pharmalot/2020/03/19/teva-mylan-coronavirus-covid19-malaria/

 

 As a result, Mylan plans to restart production of hydroxychloroquine tablets at a West Virginia facility to meet “potential” increased demand and is looking to begin manufacturing outside the U.S. in coming weeks, according to a statement. In explaining its decision, the company noted the World Health Organization listed the drug as being under investigation for combating the coronavirus.

 

He also pointed out that the University of Minnesota announced that it will start a multi-center study evaluating hydroxychloroquine in around 1,500 people who were exposed to Covid-19 within three days but are not symptomatic. And Amsellem also noted that studies are under way in South Korea and Spain.

 

And a search of PubMed, an online database of medical papers, turns up several abstracts, including “Discovering drugs to treat coronavirus disease 2019 (COVID-19),” published by three Chinese researchers in Drug Discoveries & Therapies. 

 

 

 

Fergy,

I know you mean well.

 

It depends upon the study, whether or not it should be believed.  The Chinese paper linked in the study has the following title:
"Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro" [emphasis mine]

 

"In vitro" means in a viral culture, in the lab.  Many things are effective in the lab and are not effective in people.  Many things that seem effective in small numbers of people, are not effective when tried widely.  If this was not true, the failure rate for drug candidates in clinical trials would not be as high as it is. 

 

We don't dismiss the study as "hogwash", but we look at it for what it is: an indication that the drug should be further studied in controlled clinical trials.  Which are underway.

 

China has been looking at chloroquine among other drugs and believes it to be a promising treatment (although not a cure), true - but they have not (as of yesterday) released the data they base this on.  There are more than 70 other clinical trials underway about potential therapies to treat the virus.  Some were tried anecdotally in China (anecdotally means a small number of patients treated, without controls) and had success.  You can find some links to this information about this in the Op of this Facts Only thread (I will put more up shortly; use the Singapore Saw See Hauk link).  Yes, more will be starting (including chloroquine and chloroquine/azythromycin (Zpac)  BUT WE DON'T KNOW YET.

Here is how misinformation propegates.  Exact quote of the "Published" link you highlight above:
"The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2."

So we go from "gaining traction" to "under evaluation",  from "way to shorten the severity of the virus" to "some promising results"

 

Here is a link to the full text article you cite.  Let me just give you one example of what's going on with promising treatments, including those China is using to treat:

1) the full text of the article states that the Chinese treatment guidelines recommend use of lopinavir/ritonavir:
The fifth edition of the Guidelines recommends antivirals including IFN-α, lopinavir/ritonavir, and ribavirin for treatment of COVID-19 (3)

and go on to say

Chu et al. found that lopinavir/ritonavir has anti-SARS-CoV activity in vitro and in clinical studies (6). [reference 6 is to a paper published in 2004, when Sars-CoV did not exist.  So the reference does not support the statement made about anti-SARS-CoV activity in clinical studies.  I'm not joking.  I wish I were.  By the way, I looked because in peer-reviewed scientific literature, this all too common]

 

2) This publication just in from a careful clinical trial of lopinavir/ritonavir in Wuhan Hospital China (NE Journal of Medicine, v. good journal):
A total of 199 patients with laboratory-confirmed SARS-CoV-2 infection underwent randomization; 99 were assigned to the lopinavir–ritonavir group, and 100 to the standard-care group. (in other words, it's a decent size small clinical trial and done properly).  Treatment with lopinavir–ritonavir was not associated with a difference from standard care in the time to clinical improvement. (....) Mortality at 28 days was similar in the lopinavir–ritonavir group and the standard-care group (....) The percentages of patients with detectable viral RNA at various time points were similar.

 

This is why medical experts who have seen this before are not all jumping on the bandwagon of a drug because of "promising results" or uncontrolled studies of 8 patients.  They have seen this movie before.

 

Yes, drugs with promise are out there.  Yes, clinical trials are being done.  But no, until we see data, don't jump on any bandwagons.

 

Every medical professional would LOVE ?? chloroquine or hydroxychlorquine to be the answer.  It's cheap, it's got a lot of clinical safety data in use, it's a pill, it's stable.  But until we see actual data from controlled studies, it has too many side effects to justify widespread dosing, even if we had enough warehouses full of the stuff right now.

Yes, Teva and Mylan needs to restart production of hydrochloroquine ASAP, because patients who take it daily for Lupus and other autoimmune diseases can not get their prescriptions from the drug refilled currently and are desperate. It typically takes ~ a month to validate equipment as sterile, test raw ingredients, produce the batch, and complete all the release testing; parts of this can be expedited by having techs work RTC, part can not (the reason for the mid-April timeline).  And yes, if it does prove effective, they need to start now to have enough available in a couple of months.

 

Edit: here's a link to an article about the UMN trial.  If this works, it would be big, because wiping out our HCW given the current absence of sufficient protective equipment is gonna be a huge problem

And one more edit:  Article with statements from Chinese scientist about "promising results" from Chloroquine.  100 patients is a small but OK study size. But where is the data?

 

 

[Hapless Bills Fan]

Good news front: Therapeutics

(No, not as good news as some would have you believe, but still good news)

 

This is a great link, updated regularly.  Props to @BillsFanNC for sending it.

https://sph.nus.edu.sg/wp-content/uploads/2020/03/COVID-19-Science-Report-Therapeutics-23-Mar.pdf
"A recent review of the Chinese Clinical Trial Registry identified over a hundred clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine andother medications. Traditional Chinese Medicine accounted for half of studies. There is concern that the multiple trials have been instigated rapidly and the basis and design of some may be questionable."  "A systematic review on March 17 found that only 11 have begun to recruit patients"

 

"As outlined above the WHO is sponsoring clinical trials for remdesivir; lopinavir and ritonavir; lopinavir and ritonavir plus interferon beta; and the antimalarial drug chloroquine. Some countries will test chloroquine against the standard of care while others will test hydroxychloroquine, a related drug."
 

From the CDC, advice to clinicians on therapeutic options (thanks to @GoBills808

https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html

Another article about clinical trials staring up:
https://www.upi.com/Health_News/2020/03/23/New-York-launches-new-COVID-19-drug-trials-more-underway-in-China/3681584975924/
------------------------------------------

Treatment with antibody-containing plasma - this is different, because it can be done, today.  This is a strategy that has been used successfully in other diseases (Ebola, etc)

 

***NEW!!!! ***** Promising small study published in Journal of American Medical Association (JAMA) treating critically ill patients with plasma from convalescent patients:

"In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials."

The patients were all on ventilators at the time the plasma was used, and they all showed immediate improvement.  Note that it isn't a cure, woo-hoo, they

were still on ventilators for 2 weeks - just improving,  instead of failing.

 

 

------------------------------------------------

I broke the hydroxychloroquine/azythromycin stuff into a separate post.

 

Fundamentally, the strategy for what's being tried can be summarized as "F*** ***** Up for the virus" (example of that class of drug)

-The virus is thought to bind to Angiotensin 2 (ACE2) receptors and use those to get into the lung cells.  For those who recognize the word "Angiotensin" due to blood pressure medications, BP meds target Angiotensin 1 (ACE1) receptors (confusingly, ACE1 is cleaved to ACEII.  ACEII, ACE2, not same thing).  So we're looking for ACE2 blockers (this is the point of one really fun protein docking tool available online.  OK, maybe my definition of fun is a bit "different" than some).  One clinical trial has made soluble ACE2 and is testing the effect of infusing it into the blood.  Paradoxically, it has been suggested that treating with blood pressure medications that up-regulate ACE2 might help (see link if interested).

-The virus uses its own RNA polymerase to replicate, so treat with an RNA polymerase inhibitor (favipiravir, an influenza drug; remdesivir an experimental drug for Ebola)

-The viral proteins are copied in a single long polypeptide strand, and cleaved by a protease that is part of the strand to make individual viral proteins.  HIV and other RNA viruses do something similar, so viral protease inhibitors developed for other viruses (example: lopinavir/ritonavir) are being tried.

-General antivirals -Broad-spectrum antivirals: interferon α (IFN-α), Ribavirin, Arbidol, Chloroquine

 

The leading candidates of the many examined in China seem to be interferon α, chloroquine [hydroxychloroquine], remdesivir, and favipirovir.

 

Review article by 3 Chinese scientists of therapeutics under current investigation.  Note that some of these have already fallen by the wayside; for example, while lopinavir/ritonavir (Kaletra) were part of the Chinese treatment guidelines based on local success in uncontrolled studies, a recently published study of 199 patients by Chinese scientists in New England Journal of Medicine found no difference between treated and untreated patients.  Now it may be the drugs might still work, but the active sites of HIV protease and coronavirus proteases are rather different, so this isn't unexpected.  Maybe a different dosage is needed; maybe it was given too late, when patients were too sick.

 

As of 14 March, the World Health Organization announced it would sponsor multi-national trials for 4 potential anti-covid-19 therapies.  The hope is that combining small trials with the same methodologies will yield clearer results than many small trials with different protocols.  “This trial focuses on the key priority questions for the public. Do any of these drugs reduce mortality? Do any of these drugs reduce the time a patient is in hospital and whether or not the patients receiving any of the drugs needed ventilation or intensive care units”  The drugs are remdesivir; lopinavir/ritonavir; lopinavir/ritonavir plus interferon beta; and chloroquine (or hydroxychloroquine).
 

This is important because without defining relevant outcomes, the studies might choose outcomes that don't matter as much; if the drug reduces the viral titer to zip but it doesn't reduce mortality or reduce the number of patients who need ventilators or shorten the time the patient is in hospital, well "that's nice but...."   Edit: unless it truly clears viral titer down to zippo permanently, which would potentially break the transmission chain if able to be administered widely.

(see next post)

[Hapless Bills Fan]

Good news front: Therapeutics continued

 

So what about Azythromycin (the Z-pac) and Hydroxychloroquine?

 

First of all the basis of it - why it was looked at?

The combination of azythromycin and chloroquine has been found to have a synergistic effect and be more effective against malaria than either given alone.  Azythromycin also emerged in in-vivo drug-screening tests for anti-Ebola antivirals.

 

So if one is looking at chloroquine or hydroxychloroquine therapy, it makes sense that one might test the combination.

 

How is it being looked at?
Here's the full text of the  "respected French Doctor study: touted by Dr. Oz.  I can tell you up front there are a couple of things that bother me:

1) they started out looking at hydroxychloroquine in 26 patients.  I'll quote: "Six  hydroxychloroquine-treated patients were lost in follow-up during the survey because of early cessation of treatment. Reasons are as follows: three patients were transferred to intensive care unit, including one transferred on day2  post-inclusion  who  was  PCR-positive  on  day1,  one  transferred  on  day3  post-inclusion who was PCR-positive on days1-2 and one transferred on day4 post-inclusion who was PCR-positive on day1 and day3; one patient died on day3 post inclusion:

 

Let me translate:

They initiated hydroxychloroquinine treatment in 3 patients who deteriorated and needed intensive care after 2,3, or 4 days of treatment and 1 who died.

So they were omitted from the interpretation of results - 4 patients out of 26, or 15%.  That's a lot.

 

2) 78% of the patients they looked at were healthy or had only upper respiratory symptoms - the patients that normally recover on their own.  Only 22% of the patients had lower respiratory (LRI) symptoms and pneumonia (the sick patients who are most likely to deteriorate and need ICU)  Data is not presented (that I could find) on how many of those were treated with the combination drug therapy, or information as to their clinical outcome.

3) They then co-administered azythromycin to 6 of the 20 remaining (not dead or in ICU) patients receiving hydroxyquinolone.

The end point of the study is clearing viral titer, not clinical improvement - and clearly, some of the enrollees in the study (on hydroxyquinolone alone, I think) had VERY poor outcomes.

4) The absence of error bars or a statement as to observed range in their measurements is troubling as are the vertical lines indicating p values.  That is not a "best practice" for indicating statistical significance, at least in my experience.   That said, the findings appear significant.  But the authors note: "one of the patients under hydroxychloroquine and azithromycin combination who tested negative at day6 post-inclusion was tested positive at low titer at day8 post-inclusion." (they apparently had data at longer times  they did not include! not good!)  This is why error bars matter.

 

My conclusion: This might be an important finding for clearing viral titer from asymptomatic or presymptomatic people to break the transmission chain.  If we could eliminate virus from asymptomatic or presymptomatic people, or treat exposed HCW, that would be a means to contain the virus absent a vaccine - truly  important!  I agree that their study deserved publication and the drug combination merits further study.  But it is very limited - and the statement about the viral titer being positive after 8 days when it was negative after 6 sounds a note of alarm.

 

There is not significant evidence here it is an effective treatment for serious or critical covid-19, and it is far from enough data to hail as a breakthrough or cure.  That doesn't mean it isn't, just that there is no evidence presented in this study that it is.

Edit: initial small chloroquine study in China shows no significant effect   Keep in mind it's a small study, and did not seem to look at clinical effect on seriously ill patients

https://www.bloomberg.com/news/articles/2020-03-25/hydroxychloroquine-no-better-than-regular-covid-19-care-in-study

 

New edit: larger 80-patient study from the same French group.  Fulltext preprint.
My comments for what it's worth: 

1) The conclusion that hydroxychloroquine and azythromycin may be an important strategy for viral clearance in mildly ill or asymptomatic patients is strengthened and supported by this study.  This would be big, because disease spread through asymptomatic or presymptomatic infections (or potentially, post-recovery patients) is enabling rapid spread.

2) 92% of the patients in the study had a low "NEWS" score (a metric used to assess how serious the covid-19 disease is in the patient).  Only  half (53.8%) of the patients in their study had pneumonia, let alone a stage of pneumonia that might be considered "serious".  This was NOT a study of seriously ill covid-19 patients demonstrating a cure.  To my reading, most of these patients are people whose disease would be categorized here as "mild" and they would be sent home for self-care in US or UK, not admitted to hospital.  The authors mention "The primary therapeutic objective is therefore to treat people who have moderate or severe infections at an early enough stage to avoid progression to a serious and irreversible condition" but their patient cohort, unless I am missing something, would be classed as mild disease, so they didn't demonstrate their primary objective.

3) It is an uncontrolled, unblinded study, comparing their results to a treatment group of patients in China.    There is a reason why the gold standard for assessing therapeutic efficacy is a controlled, double-blinded study, and it's not because treatments that looked promising in open, non-controlled studies pan out.
4) They were carefully screening their patients for cardiovascular problems - 12-lead EKG at Day 0 and Day 2, and they mention not initiating or discontinuing treatment if cardiovascular effects were observed, but they don't provide details of how many patients this applied to in their results section.  They state "adverse events were rare and minor", I'd just like some granularity there.
5) Once again, French Doctor peoples, PUT THE ERROR BARS ON YOUR GRAPHS.  Error bars matter.

 

On 3/23/2020 at 12:32 PM, Deranged Rhino said:

 

Guess we'll see soon enough, one way or the other. Fingers crossed. 

 

Here is what Cuomo actually tweeted:

 

Note the difference? 

 

Cuomo: FDA approved drug trials (plural, in general)

Nan Hayworth: singles out one drug treatment that may or may not work on  very sick coronavirus patients, but has been touted by President Trump (the French study linked above did not use it to treat very sick patients).

 

 

Edited March 30, 2020 by Hapless Bills Fan
Edited to add chloroquine study 30 March

[BillsFan4]

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

“Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study”

 

The antiviral used was lopinavir/ritonavir (HIV protease inhibitor)

D-dimer is a fibrin degradation product, a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis.

 

Edited March 24, 2020 by Hapless Bills Fan
add table with data

[Hapless Bills Fan]

Good news front:  Serological testing for covid-19
Q: what is serological testing?

A: serological testing looks for signs of adaptive immunity: specific antibodies that develop in response to a pathogen (covid-19 in this instance).  This type of immune response is not useful in diagnosing acute infection, because it may take several weeks to develop.

Q: why does it matter then?

If you have these antibodies, it means you have been exposed to the disease and have developed immunity.  You may have had an asymptomatic or mild case and have already recovered, or have thought what you had was "flu". 

 

Why this is crucial:

1. Doctors, Nurses, aides, and first responders will know they can safely treat covid-19 patients and will probably not become ill

2. If someone is negative for the virus itself (RT-PCR test), they can safely teach, care for elderly and patients, reenter the work force

3.. We will be able to gain info on how prevalent the disease already is or has been and build better models for how it will spread in future

4. We will identify people who may be able to donate plasma to help treat seriously ill patients.  Plasma from survivors of viral diseases has been used to treat patients in past viral outbreaks, including SARS, MERS, and Ebola.  It was used in China.  A clinical trial of treatment with immune plasma is currently underway in NYS.

 

 

Point 2. is important: some studies have shown that after being infected with covid-19, patients may continue to shed virus for 2 weeks (as long as 31 days in one report), and could potentially re-infect others.  Remember "Typhoid Mary"?  Yeah, you don't wanna be her 2020 clone.

 

This article describes development of a serology screening test at Icahn School of Medicine at Mount Sinai:

https://www.sciencemag.org/news/2020/03/new-blood-tests-antibodies-could-show-true-scale-coronavirus-pandemic

Key quote:

By indicating how much of the population is already immune because of mild infections, antibody data could offer a key to how fast the virus will continue to spread.

Such data could inform practical issues such as whether and how to reopen schools that have been closed. Relatively few cases have been diagnosed among children, but it isn’t clear whether that’s because they don’t get infected or because their infections are generally so mild that they go unnoticed. Testing children for SARS-CoV-2 antibodies should resolve that.
 

Longer term antibody tests will also help researchers understand how long immunity to the virus lasts, a key issue for any future vaccine. For other coronaviruses, Krammer notes, immunity after an infection is strong for several months, but then begins to wane. Doctors in Germany are now testing COVID-19 patients from the small cluster of cases in Bavaria in January. One month after infection, antibody levels remained high, says Clemens Wendtner, an infectious disease specialist at the Schwabing Clinic.

 

Here is a link to the preprint article describing their work
 

On 3/23/2020 at 5:51 PM, GoBills808 said:

How long from preprint to test being replicated and widely available?

 

Per the article:

It’s one of the first such detailed protocols to be widely distributed, and the procedure is simple enough, he says, that other labs could easily scale it up “to screen a few thousand people a day,” and quickly amass more data on the accuracy and specificity of the test.

Update: per this article, the researchers shipped out their protein reagent to 50 different labs.  Good work!
 

Here is an article describing use of a serology assay to track the outbreak in Singapore. 
https://www.sciencemag.org/news/2020/02/singapore-claims-first-use-antibody-test-track-coronavirus-infections
It is important because it shows that the two contacts between two clusters, who had mild symptoms that were overlooked as covid-19, had been infected.  What is more, one of the two contacts was still actively shedding virus and was immediately quarantined!

Article explaining the need for caution with antibody based tests: the antibodies don't show up for 8-14 days, and the tests need to be looked at carefully to be sure they don't cross-react with other previous infections
there is one major issue currently facing governments and healthcare authorities looking to launch similar surveillance programs. While there are an abundance of potential serological tests, such is the speed with which they have been developed and made available, no one has had the chance to check whether they really do what they say. If a particular test is faulty – for example it also yields positive results for patients who have come into contact with one of the six other strains of coronavirus known to affect humans – then the results will be at best useless, and worst, potentially lead governments to make fatally flawed decisions, such as assuming herd immunity when it isn’t actually present

Right now at the Mayo Clinic in Rochester, Minnesota, clinical microbiology director Elitza Theel and her team are one of the many centres undergoing the painstaking process of trying to work out which tests actually work, and which do not.  “It is amazing how many serological assays are coming out of the woodwork,” she says. “As well as making sure that they don’t mistakenly test positive for other diseases, we’re also ensuring that they do actually recognise Covid-19. One of the challenges and delays has been just getting the kits in because of the transportation bans.

 

[Hapless Bills Fan]

This sounds sketchy, but is actually legit.  BCG (tuberculosis vaccine) has been known for some time to have interesting effects on the immune system.

 

https://www.sciencemag.org/news/2020/03/can-century-old-tb-vaccine-steel-immune-system-against-new-coronavirus
 

Key quote about what they're doing:
Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus. They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019 and, perhaps, prevent infection with it altogether. The studies will be done in physicians and nurses, who are at higher risk of becoming infected with the respiratory disease than the general population, and in the elderly, who are at higher risk of serious illness if they become infected.

Key quote about why they think it may work:

Since then, the clinical evidence has strengthened and several groups have made important steps investigating how BCG may generally boost the immune system. Mihai Netea, an infectious disease specialist at Radboud University Medical Center, discovered that the vaccine may defy textbook knowledge of how immunity works.

When a pathogen enters the body, white blood cells of the “innate” arm of the immune system attack it first; they may handle up to 99% of infections. If these cells fail, they call in the “adaptive” immune system, and T cells and antibody-producing B cells start to divide to join the fight. Key to this is that certain T cells or antibodies are specific to the pathogen; their presence is amplified the most. Once the pathogen is eliminated, a small portion of these pathogen-specific cells transform into memory cells that speed up T cell and B cell production the next time the same pathogen attacks. Vaccines are based on this mechanism of immunity.

The innate immune system, composed of white blood cells such as macrophages, natural killer cells, and neutrophils, was supposed to have no such memory. But Netea’s team discovered that BCG, which can remain alive in the human skin for up to several months, triggers not only Mycobacterium-specific memory B and T cells, but also stimulates the innate blood cells for a prolonged period. “Trained immunity,” Netea and colleagues call it. In a randomized placebo-controlled study published in 2018, the team showed that BCG vaccination protects against experimental infection with a weakened form of the yellow fever virus, which is used as a vaccine.

Basically, they're hoping that an existing tuberculosis vaccine may boost immunity against covid-19 in doctors, nurses, and the elderly.  Now normally a vaccine against one disease doesn't produce immunity against another disease, but it's been known for a while that BCG vaccine is "different"; it's been studied as an anti-cancer therapy, for example.

Children in China and many other countries where tuberculosis and leprosy are common, are immunized with BCG vaccine routinely